ZINC HOMEOSTASIS AND KINETICS IN CHILDREN WITH CYSTIC FIBROSIS

囊性纤维化儿童的锌稳态和动力学

• 批准号: 7374987
• 负责人: IAN J GRIFFIN
• 金额: $ 5.27万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7374987
• 关键词: ZINC; HOMEOSTASIS; KINETICS; CHILDREN; CYSTIC

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Zinc is essential for normal growth, developmental and immune function. Pancreatic insufficiency is known to impair zinc absorption and overt zinc deficiency (acrodermatitis enteropathica) is well described in CF. However the importance of less severe forms of zinc deficiency is unclear due to the lack of a good measure of zinc status. The most widely used test, plasma zinc concentration, has poor specificity and sensitivity, and may be falsely depressed in CF due to co-existing infection or hypoproteinemia. We have previously shown that changes in zinc kinetics (multi-compartmental models) can identify adaptation in zinc deficiency before the plasma zinc concentration becomes abnormal. The specific objectives of this study are to compare zinc absorption, endogenous fecal zinc excretion, zinc balance and zinc status in children with CF, with and without supplementary zinc, and healthy age-matched controls. Twenty-four children with CF and pancreatic insufficiency, aged 8-14y, will be randomized to receive 20 mg/d zinc as zinc acetate or an identical placebo for 2 months. After this they will be admitted for a 6-day in-patient stay when zinc stable isotopes will be administered orally and intravenously, a complete 6-day urine and fecal collection carried out, and multiple blood samples taken after isotope administration. This data will be used to assess zinc absorption, endogenous fecal zinc excretion, zinc balance and zinc kinetics (a novel measure of zinc status). Data from the two groups of CF children will be compared to data from 12 age-matched controls consuming the current recommended daily allowance for zinc. We hypothesize that the placebo-treated CF children will have significantly lower zinc absorption, higher endogenous fecal zinc excretion, poorer zinc balance, and worse zinc status than the controls; and that the zinc-treated CF children will have similar zinc balance and zinc status to the controls. We further hypothesize that zinc supplementation will not lead to any adverse effects of iron status (hemoglobin, ferritin, transferin receptors) or copper status (serum copper, ceruloplasmin and copper- zinc superoxide dismutase). Finally, we hypothesize that fat malabsorption will be positively correlated with endogenous fecal zinc excretion, and negatively correlated with zinc absorption and zinc balance.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。锌是正常生长、发育和免疫功能所必需的。众所周知，胰腺功能不全会损害锌的吸收，明显的锌缺乏（肠病性肢端皮炎）在CF中有很好的描述。然而，由于缺乏锌状态的良好测量，不太严重的锌缺乏形式的重要性尚不清楚。目前应用最广泛的检测血浆锌浓度，其特异性和敏感性较差，在CF中可能由于同时存在感染或低蛋白血症而被错误地降低。我们之前已经证明，锌动力学的变化（多室模型）可以在血浆锌浓度异常之前识别锌缺乏的适应性。本研究的具体目的是比较CF患儿锌吸收、内源性粪便锌排泄、锌平衡和锌状态，是否补充锌，以及年龄匹配的健康对照。24名8-14岁的CF和胰腺功能不全儿童将随机接受20mg /d锌醋酸锌或相同安慰剂治疗2个月。在此之后，他们将住院6天，期间将口服和静脉注射锌稳定同位素，进行为期6天的完整尿液和粪便收集，并在同位素给药后采集多次血液样本。这些数据将用于评估锌吸收、内源性粪便锌排泄、锌平衡和锌动力学（一种新的锌状态测量方法）。来自两组CF儿童的数据将与12名年龄匹配的对照组的数据进行比较，这些对照组摄入了目前推荐的每日锌摄入量。我们假设安慰剂治疗的CF儿童的锌吸收量明显低于对照组，内源性粪便锌排泄量较高，锌平衡较差，锌状态较差；并且接受锌治疗的CF儿童的锌平衡和锌状态与对照组相似。我们进一步假设补充锌不会导致铁状态（血红蛋白、铁蛋白、转铁蛋白受体）或铜状态（血清铜、铜蓝蛋白和铜锌超氧化物歧化酶）的任何不利影响。最后，我们假设脂肪吸收不良与内源性粪便锌排泄呈正相关，与锌吸收和锌平衡负相关。